Lyme disease involves multiple organs, induding the skin, heart, joints and nervous system. Following a tick bite, 6. burgdorieri are deposited in the skin of the mammalian host. Spirochetes reside in the dermis for about one week and then spread to many tissues throughout the body. The spirochetes colonize the joints, causing arthritis in botii mice and humans. The goal of this proposal is to characterize B. /wnawtoffjerf genes important in spirochete dissemination from the skin and colonization of the iolnts. The Identified gene products will then be targeted to interfere with specific phases ofthe spirochete life cvcle. These studies will use the murine model of tick-bome fi. bu/gdbfferr infedion, which partially mimics human disease, and specimens from patients with welldocumented Lyme disease. These data will lead to a greater understanding of how fi. burgdorferi gene expression contrit>utes to spirochete infectivity, and suggest new strategies for the prevention and treatment of Lyme disease.